How does Cardizem (Diltiazem) affect ejection fraction (EF)?

How Cardizem (Diltiazem) Reduces Ejection Fraction

Diltiazem can reduce ejection fraction through its negative inotropic effects, which is why it should be discontinued in patients who develop systolic dysfunction (LVEF <50%).1

Mechanism of Action

• Diltiazem is a non-dihydropyridine calcium channel blocker that inhibits calcium influx during membrane depolarization of cardiac and vascular smooth muscle 2
• This calcium channel blockade results in:
  • Decreased sinoatrial and atrioventricular conduction in cardiac tissues 2
  • Negative inotropic effect (reduced contractility) on the myocardium 2
  • Relaxation of coronary vascular smooth muscle and dilation of coronary arteries 2

Impact on Ejection Fraction

• Diltiazem's negative inotropic properties directly reduce myocardial contractility, which can decrease left ventricular ejection fraction (LVEF) 2, 3
• The Multicenter Diltiazem Postinfarction Trial found that patients with baseline reduced ejection fraction (<40%) who received diltiazem had significantly higher rates of congestive heart failure (21%) compared to those on placebo (12%) 3
• The negative effect on ejection fraction is more pronounced in patients who already have compromised left ventricular function 3, 4

Clinical Implications

Patients with Preserved EF (≥50%)

• Diltiazem is considered appropriate for patients with preserved ejection fraction (≥50%) 1
• In patients with hypertrophic cardiomyopathy and preserved EF, diltiazem can be used to improve heart failure symptoms 1

Patients with Reduced EF (<50%)

• Diltiazem should be discontinued in patients who develop systolic dysfunction with LVEF <50% 1
• A recent study showed that patients with heart failure with reduced EF who received diltiazem despite clinical decision support warnings had a higher rate of clinical deterioration (33% vs 21%) compared to those who did not receive diltiazem 4
• These patients experienced increased need for inotropes, vasopressors, and higher rates of ICU transfer 4

Special Considerations

• Diltiazem is contraindicated in patients with:

  • Heart failure with reduced ejection fraction (HFrEF) due to its negative inotropic effects 1, 5
  • Sinus or AV conduction disease as it can worsen bradycardia 5

• For patients with atrial fibrillation and heart failure:

  • Beta-blockers are preferred over diltiazem for rate control in patients with reduced EF 1
  • In emergency settings, although diltiazem may provide faster heart rate control in atrial fibrillation with rapid ventricular response, caution is still warranted in patients with reduced EF 6

Alternative Medications for Patients with Reduced EF

• For patients with reduced EF (<50%) who need rate control:
  • Beta-blockers should be considered as first-line therapy 1
  • ACE inhibitors or ARBs should be added to beta-blockers 1
  • Low-dose loop diuretics should be considered for symptomatic patients 1
  • Mineralocorticoid receptor antagonists (MRAs) should be considered for persistent symptoms 1
  • Low-dose digoxin may be considered for patients with permanent atrial fibrillation 1

By understanding diltiazem's negative inotropic effects, clinicians can make appropriate decisions about its use based on a patient's ejection fraction and overall cardiac function.